P1616: NGS-BASED PATHOGEN DIAGNOSTIC IN FEBRILE HAEMATOLGY PATIENTS – A SINGLE-CENTRE EXPERIENCE
Authors: S. Wolf, C. S. Schmidt, T. M. Schmitt, E. Siegel, C. Hamm, P. Stevens, M. Theobald, D. Teschner
Journal: HemaSphere (2022)

Background: Bloodstream infections are frequent and serious complications in immunocompromised patients mainly in haemato- and oncology. The established gold standard in pathogen diagnostic for microbial infections is the analysis of blood cultures (BC). By BC, bacterial pathogens can be detected in approximately 30% of blood samples from neutropenic patients only. Additionally, viral or fungal infections are even more challenging to detect and require special procedures or invasive diagnostics. To close this diagnostic gap and to increase the yield of pathogen detection, NGS-based approaches were developed to detect cell-free DNA in plasma samples and evaluate the findings using elaborated mathematical algorithms. Aims: The aim of this study was to compare the new NGS-based diagnostic approach with established conventional microbial diagnostic in febrile high-risk cancer patients. Methods: In a first step, patients covered by selected health insurances were included in the analysis after informed consent between September ‘20 and July ‘21. Afterwards, all patients with a related underlying disease were included between August ’21 and November ’21. From these patients, blood samples were drawn during a first episode of fever. These blood samples were analysed by NGS-based DISQVER®-diagnostic developed and performed by Noscendo GmbH. Addition, conventional pathogen diagnostic was performed according to our local standard of care. This includes mainly BCs but also specific viral or histopathologic diagnostic, when clinically indicated. The analysis of conventional diagnostic samples was performed by our Institute of Clinical Microbiology. After analysis, we reviewed the different results and correlated them with clinical information’s and vice versa. Results: Diagnostic Samples were collected in a total of 71 febrile episodes (events) in 47 patients. In these patients, an underlying malignant hematologic disease was present in n=67 (87%). 30 events (42%) were post allogeneic stem cell transplantation. Neutropenia (granulocyte count <500/µl) was present during 37 febrile episodes (51%). Overall, microbial pathogen detection could be obtained in 45/71 events (63%). In 25/71 febrile episodes (35%), pathogens were detected by NGS-based diagnostic only and the corresponding conventional diagnostics remained negative. Positive conventional and positive NGS-based diagnostic were present in 18 events. In these, identical pathogens were detected NGS-based and in the corresponding BC only in 4 events while in the remaining 14 febrile episodes conventional pathogens could only be identified by additional assays or more invasive diagnostic procedures (endoscopy, biopsy and others). In 2 events, pathogens were detected by conventional diagnostics but NGS-based was negative. Overall, 42 different pathogens could be identified by NGS-based diagnostic (24 bacterial, 12 viral and 6 fungal pathogens [including zygomycetes]). Summary/Conclusion: In our study, combination of NGS-based and conventional microbial diagnostic identified substantially more pathogens than conventional diagnostic alone. Moreover, NGS-based diagnostic revealed a higher sensitivity and diagnostic yield compared to conventional and even more invasive diagnostic approaches. Additionally, the NGS-based diagnostic approach seems to detect more and/or even difficult-to-detect microbial pathogens compared to standard diagnostic procedures. However, not every NGS-based detected pathogen turned out to be clinically relevant and led to a therapeutic consequence.